scholarly journals High plasma concentration of non-esterified polyunsaturated fatty acids is a specific feature of severe COVID-19 pneumonia

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Maxime Nguyen ◽  
◽  
Abderrahmane Bourredjem ◽  
Lionel Piroth ◽  
Bélaïd Bouhemad ◽  
...  

AbstractCOVID-19 pneumonia has specific features and outcomes that suggests a unique immunopathogenesis. Severe forms of COVID-19 appear to be more frequent in obese patients, but an association with metabolic disorders is not established. Here, we focused on lipoprotein metabolism in patients hospitalized for severe pneumonia, depending on COVID-19 status. Thirty-four non-COVID-19 and 27 COVID-19 patients with severe pneumonia were enrolled. Most of them required intensive care. Plasma lipid levels, lipoprotein metabolism, and clinical and biological (including plasma cytokines) features were assessed. Despite similar initial metabolic comorbidities and respiratory severity, COVID-19 patients displayed a lower acute phase response but higher plasmatic concentrations of non-esterified fatty acids (NEFAs). NEFA profiling was characterised by higher level of polyunsaturated NEFAs (mainly linoleic and arachidonic acids) in COVID-19 patients. Multivariable analysis showed that among severe pneumonia, COVID-19-associated pneumonia was associated with higher NEFAs, lower apolipoprotein E and lower high-density lipoprotein cholesterol concentrations, independently of body mass index, sequential organ failure (SOFA) score, and C-reactive protein levels. NEFAs and PUFAs concentrations were negatively correlated with the number of ventilator-free days. Among hospitalized patients with severe pneumonia, COVID-19 is independently associated with higher NEFAs (mainly linoleic and arachidonic acids) and lower apolipoprotein E and HDL concentrations. These features might act as mediators in COVID-19 pathogenesis and emerge as new therapeutic targets. Further investigations are required to define the role of NEFAs in the pathogenesis and the dysregulated immune response associated with COVID-19.Trial registration: NCT04435223.

Author(s):  
Rajat Gupta ◽  
Yan Lin ◽  
Karla Luna ◽  
Anjali Logue ◽  
Alexander J Yoon ◽  
...  

Rationale: Chronic electronic cigarette (EC) users exhibit a higher susceptibility of low-density lipoprotein (LDL) to undergo oxidation as compared to non-user controls. However, there is a paucity of data regarding EC effects on lipid peroxidation in the blood and their relationship to cardiovascular risk. Objective: To test the hypothesis that chronic (≥1 year) EC use exerts intermediate effects on plasma lipid peroxidation and/or antioxidant defense compared to chronic tobacco cigarette (TC) smoking. Methods and Results: We enrolled EC-users (n=32), TC-smokers (n=29) and non-users (n=45), with mean ages of 28.3, 27.8 and 27.4 years, respectively. Plasma concentrations of free polyunsaturated fatty acids and oxidized metabolites were assessed by mass spectrometry. Total antioxidant capacity (TAC), concentrations of glutathione, bilirubin, heme oxygenase-1 (HO-1), and functional activity of paraoxonase1 (PON1) were determined by colorimetric and enzymatic assays. Multivariable analysis was performed using classification models for segregating participants based on biomarker profiles. Plasma arachidonic acid (AA) concentration was higher in TC-smokers but lower in EC-users, together with linoleic acid (LA) concentration, as compared to TC-smokers and non-users (p<0.05). Oxidized LA metabolites (9- and 13-hydroxyoctadecadienoic acid (HODE)) were lower in EC-users and TC-smokers as compared to non-users (p<0.001). Consistently, TAC and bilirubin were elevated in EC-users and TC-smokers as compared to non-users (p<0.05). Of interest, plasma HO-1 concentration was higher in TC-smokers as compared to non-users (p=0.01) with intermediate levels in EC-users. Multivariable analysis identified 5 biomarkers (13-HODE, LA, 9-HODE, 12-hydroxyeicosatetraenoic acid (HETE), AA) that discriminated EC-users from TC-smokers and non-users with an accuracy of 73.4%. Conclusions: Chronic use of EC induces common (i.e. lower 9- and/or 13-HODEs and higher TAC and bilirubin) as well as differential effects (i.e. altered AA and LA concentrations) to those induced by TC, along with intermediate plasma HO-1 concentration, suggesting that EC, likewise TC smoke, could impact cardiovascular risk.


1995 ◽  
Vol 311 (1) ◽  
pp. 167-173 ◽  
Author(s):  
A J Bennett ◽  
M A Billett ◽  
A M Salter ◽  
E H Mangiapane ◽  
J S Bruce ◽  
...  

Different dietary fatty acids exert specific effects on plasma lipids but the mechanism by which this occurs is unknown. Hamsters were fed on low-cholesterol diets containing triacylglycerols enriched in specific saturated fatty acids, and effects on plasma lipids and the expression of genes involved in hepatic lipoprotein metabolism were measured. Trimyristin and tripalmitin caused significant rises in low-density lipoprotein (LDL) cholesterol which were accompanied by significant reductions in hepatic LDL receptor mRNA levels. Tripalmitin also increased hepatic expression of the apolipoprotein B gene, implying an increased production of LDL via very-low-density lipoprotein (VLDL) and decreased removal of LDL in animals fed this fat. Hepatic levels of 3-hydroxy-3-methylglutaryl-CoA reductase mRNA did not vary significantly between the groups. Compared with triolein, tristearin had little effect on hepatic gene expression or total plasma cholesterol. However, it caused a marked decrease in VLDL cholesterol and a rise in LDL cholesterol such that overall it appeared to be neutral. Lipid analysis suggested a rapid desaturation of much of the dietary stearate. The differential changes in plasma lipids and hepatic mRNA levels induced by specific dietary fats suggests a role for fatty acids or a metabolite thereof in the regulation of the expression of genes involved in lipoprotein metabolism.


Marine Drugs ◽  
2020 ◽  
Vol 18 (6) ◽  
pp. 292 ◽  
Author(s):  
Federica Fogacci ◽  
Enrico Strocchi ◽  
Maddalena Veronesi ◽  
Claudio Borghi ◽  
Arrigo F. G. Cicero

Even though omega-3 polyunsaturated fatty acids (PUFAs) seem to be effective in the treatment of human immunodeficiency virus (HIV)-associated dyslipidemia, their impact is still debated. For this reason, our aim was to perform a meta-analysis of the clinical evidence available to date. A systematic literature search was conducted in order to identify published clinical trials assessing the effect of PUFAs treatment on serum lipoproteins, and its safety profile. The effect sizes for lipid changes were expressed as mean difference (MD) and 95% confidence interval (CI). For safety analysis, odd ratios and the 95% CI were calculated with the Mantel–Haenszel method. Data were pooled from nine clinical studies comprising overall 578 HIV-affected subjects. Meta-analysis of the data suggested that omega-3 PUFAs significantly reduced triglycerides (TG) (MD = −1.04, 95% CI: −1.5, −0.58 mmol/L, p < 0.001), while increasing high-density lipoprotein cholesterol (MD = 0.36, 95% CI: 0.12, 0.61 mmol/L, p = 0.004), without affecting serum levels of total cholesterol, very-low- and low-density lipoprotein cholesterol, and apolipoprotein B and A1. Change in TG was significantly associated with eicosapentaenoic acid administered via daily dose. PUFA treatment did not lead to an increased risk of adverse events. In conclusion, PUFAs are safe and exert a significant plasma lipid improving effect in HIV-positive patients.


1992 ◽  
Vol 82 (6) ◽  
pp. 701-708 ◽  
Author(s):  
G. L. Warwick ◽  
C. J. Packard ◽  
L. Murray ◽  
D. Grierson ◽  
J. P. Stewart ◽  
...  

1. The effect of inhibiting the rate-limiting enzyme (3-hydroxy-3-methylglutaryl-CoA reductase, EC 1.1.1.88) in cholesterol synthesis on plasma lipid and lipoprotein concentrations was investigated in 16 patients with primary glomerular disease, heavy proteinuria, well-preserved renal function and hypercholesterolaemia. 2. Detailed studies of low-density lipoprotein metabolism were performed on eight patients before and after 12 weeks of simvastatin therapy. Radioiodinated tracers were used to quantify the fractional catabolic rate of low-density lipoprotein by apolipoprotein B/E receptors and alternative pathways. 3. Simvastatin produced consistent reductions in total plasma cholesterol concentration (median 36.9%), plasma low-density lipoprotein-cholesterol concentration (43.6%) and apolipoprotein B pool size (29.9%). 4. In contrast, the changes in kinetic parameters of low-density lipoprotein metabolism showed no clear pattern. Although an increase in the receptor-mediated catabolism of low-density lipoprotein was demonstrated in five patients, no change or a slight decrease was seen in three patients. Production rates were not significantly altered, although there was a slight decrease in the median value (from 12.4 to 9.7 mg day−1 kg−1). Plasma lathosterol concentration was reduced in all eight patients (range 34–71%), indirectly confirming significant inhibition of cholesterol synthesis. 5. These results suggest that, as in patients with primary moderate hyperlipidaemia, the significant cholesterol-lowering effect of 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors in the nephrotic syndrome is accompanied by variable changes in lipoprotein metabolism. The reasons for this heterogeneous response are unclear. This reflects our limited understanding of the metabolic basis of nephrotic hyperlipidaemia and the relationship between hepatic sterol synthesis and plasma lipoprotein kinetics.


2010 ◽  
Vol 95 (7) ◽  
pp. 3377-3384 ◽  
Author(s):  
Faidon Magkos ◽  
Elisa Fabbrini ◽  
B. Selma Mohammed ◽  
Bruce W. Patterson ◽  
Samuel Klein ◽  
...  

Context: Sex differences in lipid metabolism result in a less proatherogenic plasma lipid profile in premenopausal women than men. The mechanisms responsible for this are unclear but are thought to be related to differences in the sex hormone milieu in men and women. Objective: Our objective was to evaluate the effect of endogenous sex hormones on very-low-density lipoprotein (VLDL) triglyceride (TG) and apolipoprotein B-100 (apoB-100) metabolism. Experimental Design and Main Outcome Measures: We measured basal VLDL-TG and VLDL-apoB-100 concentrations and kinetics by using stable isotope-labeled tracers. Setting and Participants: Eight premenopausal women [age, 43 ± 8 yr; body mass index (BMI), 35 ± 4 kg/m2; mean ± sd], eight postmenopausal women (age, 55 ± 4 yr; BMI, 34 ± 4 kg/m2), and eight men (age, 41 ± 13 yr; BMI, 34 ± 4 kg/m2) were studied at Washington University School of Medicine, St. Louis, MO. Results: VLDL-TG secretion rate was approximately double (P &lt; 0.05) in postmenopausal women and men compared with premenopausal women but not different in postmenopausal women and men. The secretion rate of VLDL-apoB-100 was not different in pre- and postmenopausal women but was greater (P &lt; 0.05) in men than in women. Conclusions: Endogenous ovarian sex steroids are responsible for sexual dimorphism in VLDL-TG secretion, whereas VLDL-apoB-100 secretion is not regulated by female reproductive hormones.


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